Marrow cell egress. The central interaction of barrier pore size and cell maturation.

Abstract

Release of marrow cells may be determined primarily by the restrictive barrier that separates marrow hematopoietic cords from sinusoids, and by the ability of the cell to negotiate the barrier pores which are of smaller diameter than the cell. This critical interrelationship may be further modulated by humoral agents (releasing factors). To test this hypothesis, we placed human marrow cells in a chamber between millipore or nucleopore filters with pore diameters of 1-8 mum. Fixed, stained, cross sections of the filters allowed histological examination of the penetration of cells and quantification of egress of age-specific cell types. The rate of marrow granulocyte egress was highly correlated with (a) barrier pore diameter. (b) morphological age of cells, and (c) the presence of chemical attractant. Immature granulocytes would not exit through a restrictive barrier even after protracted periods and were not responsive to chemoattractants. Intermediate-aged granulocytes showed a slight ability to respond to attractants and to exit if pore diameters were large. Mature granulocytes exited through the restrictive barrier at all pore diameters studied, however, this egress was accelerated by increasing pore diameter and by the presence of an attractant. Leukemia blast cells were incapable of traversing pore diameters of 1-8 mum.These studies support the hypothesis that the development of deformability, motility, and surface receptors for chemoattractants at the later stages of granulocyte development allow the egress of cells through the marrow sinusoid wall which appears by electron microscopy to be a porous barrier with aperture diameters smaller than cell diameters; and that this process can be modulated by humoral agents which enhance directed movement of cells and may also increase pore size. Moreover, on the basis of our observations, the egress of leukemia cells is best explained by destruction of the normal sinusoid barrier of marrow indicating that manifestations of the disease are dependent on alteration in stromal as well as parenchymal marrow cells.